A multi-omics study to investigate the progression of the Correa pathway in gastric mucosa in the context of cirrhosis.

IF 4.3 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Ruiguang Ma, Qian Li, Guoxian Yu, Jun Wang, Yueyue Li, Xinyan Xu, Yiqing Zhu, Min Dong, Yanjing Gao, Lixiang Li, Zhen Li
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Abstract

Background: Patients with liver cirrhosis (LC) are prone to gastric mucosa damage. We investigated the alterations of gastric mucosa in LC patients and their possible mechanisms through multi-omics.

Results: We observed significant gastric mucosa microbial dysbiosis in LC subjects. Gastric mucosal microbiomes of LC patients contained a higher relative abundance of Streptococcus, Neisseria, Prevotella, Veillonella, and Porphyromonas, as well as a decreased abundance in Helicobacter and Achromobacter, than control subjects. The LC patients had higher levels of bile acids (BAs) and long-chain acylcarnitines (long-chain ACs) in serum. The gastric mucosal microbiomes were associated with serum levels of BAs and long-chain ACs. Transcriptome analyses of gastric mucosa revealed an upregulation of endothelial cell specific molecule 1, serpin family E member 1, mucin 2, caudal type homeobox 2, retinol binding protein 2, and defensin alpha 5 in LC group. Besides, the bile secretion signaling pathway was significantly upregulated in the LC group.

Conclusions: The alterations in the gastric mucosal microbiome and transcriptome of LC patients were identified. The impaired energy metabolism in gastric mucosal cells and bile acids might aggravate the inflammation of gastric mucosa and even exacerbate the Correa's cascade process. The gastric mucosal cells might reduce bile acid toxicity by bile acid efflux and detoxification.

Trial registration: ChiCTR2100051070.

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一项研究肝硬化背景下胃黏膜Correa通路进展的多组学研究。
背景:肝硬化(LC)患者易发生胃黏膜损伤。我们通过多组学研究了LC患者胃黏膜的变化及其可能的机制。结果:我们在LC受试者中观察到显著的胃黏膜微生物微生态失调。LC患者的胃粘膜微生物群中链球菌、奈瑟菌、普雷沃氏菌、韦氏菌和卟啉单胞菌的相对丰度高于对照组,而幽门螺杆菌和无色杆菌的丰度则较低。LC患者血清中胆汁酸(BA)和长链酰基肉毒碱(AC)水平较高。胃粘膜微生物群与血清中BA和长链AC的水平有关。胃粘膜的转录组分析显示,LC组内皮细胞特异性分子1、serpin家族E成员1、粘蛋白2、尾型同源盒2、视黄醇结合蛋白2和防御素α5上调。此外,LC组胆汁分泌信号通路显著上调。结论:LC患者的胃黏膜微生物组和转录组发生了改变。胃黏膜细胞和胆汁酸的能量代谢受损可能加剧胃黏膜炎症,甚至加剧Correa级联过程。胃粘膜细胞可能通过胆汁酸的流出和解毒来降低胆汁酸的毒性。试验注册号:ChiCTR2100051070。
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来源期刊
Gut Pathogens
Gut Pathogens GASTROENTEROLOGY & HEPATOLOGY-MICROBIOLOGY
CiteScore
7.70
自引率
2.40%
发文量
43
期刊介绍: Gut Pathogens is a fast publishing, inclusive and prominent international journal which recognizes the need for a publishing platform uniquely tailored to reflect the full breadth of research in the biology and medicine of pathogens, commensals and functional microbiota of the gut. The journal publishes basic, clinical and cutting-edge research on all aspects of the above mentioned organisms including probiotic bacteria and yeasts and their products. The scope also covers the related ecology, molecular genetics, physiology and epidemiology of these microbes. The journal actively invites timely reports on the novel aspects of genomics, metagenomics, microbiota profiling and systems biology. Gut Pathogens will also consider, at the discretion of the editors, descriptive studies identifying a new genome sequence of a gut microbe or a series of related microbes (such as those obtained from new hosts, niches, settings, outbreaks and epidemics) and those obtained from single or multiple hosts at one or different time points (chronological evolution).
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